Red Blood Cell Polyamine Research Articles

Changes in blood polyamine levels in human acute pancreatitis

Objective. Experimental studies have shown that pancreatic activation of polyamine catabolism occurs during the early stage of acute pancreatitis. Changes in pancreatic polyamines are reflected in the red blood cell (RBC) polyamine contents, correlating with the extent of pancreatic necrosis. The aim of this human study was to examine the changes in polyamine levels in the RBCs of patients with acute pancreatitis. Material and methods. Twenty-four patients with acute pancreatitis (7 alcoholic, 10 gallstone and 7 of unknown etiology) were recruited in the study. Eighteen patients with non-pancreatic acute abdominal diseases were included as controls, and 6 volunteers were studied as references. Blood samples were collected on admission and during hospitalization to assess polyamine levels. After clinical recovery, the patients revisited the clinic, and RBC polyamine levels were measured again. For comparison, plasma interleukin-6 (IL-6), IL-10 and C-reactive protein (CRP) were measured. Results. In acute pancreatitis patients, there was no difference in RBC polyamine levels on admission compared with those in controls or in volunteers. Putrescine levels on admission were higher in patients with pancreatic necrosis than in patients without necrosis, but there was no difference in spermidine and spermine levels. Patients with pancreatitis of unknown etiology had significantly higher levels of polyamines on admission and throughout hospitalization, but they also had more necrosis, which explained the difference in multivariate analysis. Spermidine and spermine levels increased after clinical recovery. RBC putrescine correlated with IL-6 and IL-10, and spermine correlated with CRP. Conclusions. The results of this study suggest that RBC polyamines change in human acute pancreatitis in several respects, as has been previously observed in experimental pancreatitis.

Polyamine Levels in the Pancreas and the Blood Change according to the Severity of Pancreatitis

Background/Aims: Polyamines are essential to survival, growth, and proliferation of mammalian cells. Previous studies have suggested that the pancreatic polyamine levels may change in acute pancreatitis. In this study, the changes of polyamine levels in the pancreas have been studied with respect to the severity of pancreatitis. We investigated whether there is a relationship in polyamine levels between pancreas and blood, and whether pancreatic and blood polyamine levels change according to the severity of pancreatitis. Methods: In rats, sublethal pancreatitis was induced by intraductal infusion of 2% taurodeoxycholate, while lethal pancreatitis was induced with 6% taurodeoxycholate. Results: Infusion of 6% taurodeoxycholate as compared with 2% resulted in more severe pancreatitis, as revealed by mortality, histology, and serum amylase activity. Pancreatic spermidine/spermine N1-acetyltransferase was induced early after pancreatitis and was associated with increased putrescine and decreased spermidine levels. The extent of pancreatic necrosis significantly correlated with the polyamine catabolism indicators pancreatic putrescine/spermidine ratio (r = 0.29, p < 0.01) and pancreatic putrescine/spermine ratio (r = 0.32, p < 0.01). The two pancreatic polyamine ratios correlated well also with the red blood cell polyamine ratios (r = 0.75 and r = 0.72, respectively, both p < 0.01). Furthermore, the extent of pancreatic necrosis correlated with red blood cell putrescine/spermidine (r = 0.32, p < 0.01) and putrescine/spermine (r = 0.37, p < 0.01) ratios. Conclusions: Acute experimental pancreatitis is associated with an early pancreatic spermidine/spermine N1-acetyltransferase induction and consequent changes in polyamine levels in pancreas and red blood cells, depending on the severity of pancreatitis. Because changes in red blood cell spermidine, spermine, and putrescine levels evolve already early during the time course of pancreatitis, and correlate with the extent of pancreatic necrosis, their clinical value as early markers of the severity of acute pancreatitis needs to be further evaluated. Copyright © 2008 S. Karger AG, Basel and IAP

Effects of human growth hormone (hrGH) treatment on amine metabolism in rats subjected to extensive small bowel resection.

The effect of human recombinant growth hormone (hrGH) on intestinal adaptation in rats subjected to massive small bowel resection has been followed by monitoring changes in the tissue polyamine system and in red blood cell (RBC) polyamine levels. In parallel, the activities of monoamine oxidase A and B and diamine oxidase, the enzymes that catalyse one of the major routes of biogenic amine metabolism, oxidative deamination, were also examined. The results suggest that whilst hrGH treatment accelerates adaptive intestinal hyperplasia evoked by the resection, it has no significant effect on RBC polyamine level or gut mucosal DNA concentration as measured 3 weeks post surgery. hrGH treated operated rats exhibited significantly lower amine oxidase activities which implies that GH may alter biogenic amine systems.

Increased Red Blood Cell Polyamines in ALS and Parkinson's Disease

The polyamines spermidine (SPD) and spermine (SPM) are implicated in nerve cell degeneration and regeneration. Over 70% of circulating polyamines are associated with red blood cells (RBC). Against this background we have analysed RBC polyamines in two neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Twenty patients with the sporadic form of ALS, 20 patients with PD, and 20 healthy controls were studied. The highest levels of SPD and SPM were found in the PD group where the mean values were 134 and 115%, respectively, above those of the controls. The patients with PD also presented the lowest levels of the SPD precursor, putrescine (PUTR). In the patients suffering from ALS the SPD and SPM mean levels were increased by 46 and 112%, respectively. The RBC SPD/SPM ratio in the patients suffering from PD was significantly elevated in comparison with that of ALS patient group, suggesting a different involvement of the polyamine system in these disorders. It is at present unknown if raised polyamine levels may contribute to induce the degeneration of susceptible neurons or if the increase represents a compensatory protective reaction, or simply an unspecific epiphenomenon.

Relationship among red blood cell polyamine content, phagocytic activities and plasma endotoxins in untreated colorectal cancer patients.

Polyamines are actively involved in immune processes and it is known that patients with cancer often exhibit immune deficits. Twenty-two patients with colorectal cancer were enrolled into this study, before starting conventional treatments. The relationship among the content of polyamines in red blood cells and phagocytosis and killing of monocytes and polymorphonuclear cells, and endotoxemia was investigated. The data show a negative correlation among levels of total polyamines and spermine and monocyte phagocytosis. Higher levels of spermine were present in patients with detectable circulating endotoxins. Our findings suggest a down-modulating effect of polyamines on the monocyte phagocytosis in untreated colorectal cancer patients; this effect could explain the presence of circulating endotoxins in cancer bearing patients.

Red blood cell poly amines, anaemia and tumour growth in the rat

In rats with Mat Lylu prostatic carcinoma, significant changes in blood composition and red blood cell (RBC) characteristics were observed. Anaemia, characterised by a decrease in the number of RBC and the reduction of haemoglobin and the iron content in plasma, was correlated with tumour size and the accumulation of spermidine and spermine in the RBC. In large tumours, spermidine levels were increased by 8-fold over normal value. Spleen weight and splenic spermidine concentrations were enhanced in animals with tumours. After splenectomy, the rate of tumour growth decreased by 30%. It is proposed that anaemia in tumour-bearing animals is caused by enhanced RBC lysis, owing to the alteration of the rheological properties of RBC. These may be caused by the alterated surface characteristics due to polyamine accumulation. RBC lysis and high concentrations of polyamines in RBC and spleen appear, not only to favour tumour growth, but also to compromise the immunological defence mechanisms against neoplastic invasion.

P-490 Polymerase chain reaction analysis of hepatitis B virus DNA sequences in hepatocellular carcinomas from patients negative for hepatitis B surface antigen and positive for anti-HCV antibody

The present study tries to evaluate the diagnosit value in malignant hepatic tumors of polyamines, of which the relationship with cellular kinetics is known, and histamine, of which catabolism follows a similar pathway. One hundred and fifty six patients were studied: 53 with malignant liver tumors (27 primary, 26 metastatic) and 103 with non-tumoral liver diseases of which 65 were cirrhotic and 38 non-cirrhotic. Erythrocyte polyamines (spermidine and spermine) and histamine levels were assayed. The results indicate the following. 1. Polyamine levels were significantly increased (a) in cirrhotic patients, not only when compared with controls (p < 10−8), but also when compared with the non-cirrhotic patients (p < 10−7); (b) in primary malignant hepatic tumors (p < 10−3). 2. Histamine was significantly increased (a) in the non-tumoral liver diseases (p < 10−4), but with no difference between cirrhotic and non-cirrhotic patients; (b) in the secondary malignant tumor patients, histamine levels were lower than in primary tumor patients (p < 0.04). 3. There was no correlation, in all groups studied, between polyamine and histamine levels.These results suggest the following practical implications. 1. For non-tumor liver diseases, appreciably increased polyamine levels may represent a further argument favoring a cirrhotic condition. 2. In diagnosing hepatic scintigraphic defects, inbetween histamine and polyamines, are in favor of histamine synthesis. In the secondary malignant hepatic tumor group, histamine levels were low. sometimes considerably. Future studies, by estimating plasma diamine oxidase activity may he able to solve some of these questions.In conclusion, the evaluation of erythrocyte polyamine and histamine levels has two practical implications in hepatology. For non-tumor liver diseases, appreciably increased red blood cell polyamine levels may represent a further argument favoring a cirrhotic condition. In diagnosing hepatic scintigraphic defects, increased erythrocyte polyamine levels would suggest a primary malignant hepatic tumor; low histamine levels are more in favor of a secondary malignant hepatic process.

Standardization in the determination of red blood cell polyamines by high-performance liquid chromatography

The choice of the standardization method in the high-performance liquid chromatographic determination of dansyl polyamines (spermidine and spermine) in red blood cell extracts is discussed. 1,6-Hexanediamine, commonly used as an internal standard, is unsuitable for the quantification of spermidine and spermine in red blood cells because their percentage recoveries are significantly different (100% for 1,6-hexanediamine, and 70% for spermidine and spermine). The external standard method and the standard addition method are better suited. The procedure for the preparation of the standard mixture before dansylation has an influence on the values of red blood cell polyamines. Two procedures are compared and the corresponding percentages of variation were found to be high for spermidine and spermine. Thus the procedure in which the standard is treated in a strictly similar way as the red blood cells is certainly the most appropriate one for the quantification.

On the degradation and elimination of spermine by the vertebrate organism

1.1. Treatment of mice and rats with the polyamine oxidase inhibitor N1,N4-bis-(2,3-butadienyl)- 1, 4-butanediamine (MDL 72527) causes a gradual accumulation of spennine in the circulation and a decrease of spennidine concentration.2.2. Spennine is mainly localized in the red blood cells.3.3. Co-administration of 2-(dinuoromethyl)omithine and MDL 72527 enhances considerably the rate and extent of spennine accumulation in the circulation.4.4. It is assumed that the increased rate of spennine accumulation by the two drugs is due to the enhancement of cell death, i.e. spennine accumulation is the result of its release into the circulation from dying cells, not due to physiological release.5.5. After discontinuation of polyamine oxidase inhibition spennine appears to be gradually transformed into spennidine by red blood cell polyamine oxidase, obviously without transformation into N1-acetylspennine.

Erythrocyte Polyamine Levels in Human Prostatic Carcinoma

Abnormally high red blood cell polyamine levels were found in benign prostatic hyperplasia and in prostatic adenocarcinoma patients. In prostatic adenocarcinoma patients a relationship was noted between the importance of red blood cell spermidine and spermine concentrations, and the clinical stage of the disease (Whitmore classification). Considering prostatic adenocarcinoma patient populations, patients with metastases (groups 3 and 4) statistically differed from those without metastases (group 2). Furthermore, red blood cell polyamine level determination discriminated patients in the hormonal escape group (group 4) from those usually considered as hormone responsive (groups 2 and 3). No statistically significant correlation was observed between red blood cell polyamine levels and usual tumor markers (prostatic acid phosphatase and prostate specific antigen). These results confirmed that red blood cell polyamine levels must be considered as a circulating index of cell proliferation that might be of clinical importance during the long-term followup and treatment of prostatic adenocarcinoma patients. (J. Urol., 144: 1164–1166, 1990)

Polyamine levels in red blood cells from patient groups of different sex and age

Interpretation of polyamine levels found in the tissues and red blood cells of tumour patients has been plagued by the wide variations seen in the concentrations when estimated in groups of either tumour or control patients. To ascertain whether the patient's age or sex were contributing factors, red blood cell polyamine concentrations of 117 control patients were examined by high-performance liquid chromatography. Concentrations of spermidine were consistently higher than those of spermine. Also, regression analysis showed that spermidine and spermine levels tended to change with age and sex, though these trends were statistically non-significant.

Variations in red blood cell polyamines in brain tumour patients treated with stereotactic radiosurgery

Red blood cell polyamine levels were followed in 13 patients treated with stereotactic radiosurgery for various types of brain tumours. In the most malignant tumours radiosurgery resulted in a decrease in spermine and an increase in spermidine levels. This discrepancy between variations in polyamine levels was not found after conventional radiotherapy. The results may indicate a change in tumour polyamine activity induced by high energy radiotherapy.

Red blood cell polyamines as a diagnostic indicator of glioma presence and recurrence.

Red blood cell (RBC) polyamines, spermine and spermidine have been assayed from 103 patients with confirmed intracranial tumours and 87 controls. For spermine the test had a specificity of 97% and a sensitivity of 30% in preoperative patients, increasing to 40% in glioma patients. Tumour recurrence in postoperative patients gave a sensitivity of 48% increasing to 60% in glioma groups. For initial tumour presentation, therefore, this test is suggestive, though not unequivocal, of tumour presence. Its major role probably lies in monitoring the progress of the patient and its major importance in the detection of tumour recurrence.

Red blood cell polyamines in brain tumour patients.

Red blood cell polyamine levels have been determined in patients with various histologically confirmed brain tumours. Increased spermine and spermidine levels were found in most patients with perifocal oedema demonstrated by CT; no correlation was found to other CT variables, nor to tumour localization. Polyamine levels increased during the clinical course coincident with tumour activity and decreased in response to surgery and radiotherapy. The response to chemotherapy involved a change in the relationship between spermine and spermidine levels. Our results underline the significance of regular polyamine level estimation during the management of patients with brain tumours.

Evolution of red blood cell polyamine levels in partially hepatectomized rat

Erythrocyte levels of polyamines, especially of spermidine are greatly elevated during the course of liver regeneration. In contrast to putrescine and spermine levels, from the tenth hour to the fourth week after partial hepatectomy, correlation has been observed between the elevation of liver and erythrocyte spermidine concentrations. Substituting drinking water with 2% α difluoromethylornithine (α-DFMO) commencing 48 hr prior to partial hepatectomy and continuing until death, though ineffective in inhibition of liver [ 3H]-thymidine incorporation, prevented the rise in hepatic putrescine concentrations (without modifying those of spermidine and spermine) and correlatively decreased red blood cell (RBC) spermidine levels. Thus, an excess of liver spermidine produced from an excess of newly synthetized putrescine could be released in blood and taken up by erythrocytes, especially as affinity of RBC for spermidine is at least 30 fold higher than that for putrescine. In vivo the spermidine half-life in RBC was estimated to be 2.5–3.0 hr, which could explain the elevation of erythrocyte and liver spermidine levels. The elevation of erythrocyte spermidine concentration is not correlated to that of the regenerating liver weight but dependent on the extent of partial hepatectomy. The elevation of erythrocyte spermidine concentrations, which appeared to be linked to the cellular proliferating activity, could contribute to determine intratumoral proliferation in cancerous patients.

Red blood cell polyamine levels and host toxicity during continuous alpha-difluoromethylornithine infusion.

The dose effects of continuous alpha-difluoromethylornithine (DFMO) infusion on red blood cell (RBC) polyamine levels, host toxicity and tumor growth were determined. Male rats with and without a transplantable methylcholanthrene-induced sarcoma received intravenously either 0.45% NaCl or DFMO at 500 mg, 1,000 mg, or 2,000 mg/kg body wt/day for 6 or 12 days. Dose-related inhibition of tumor growth was noted after the 12-day treatment. There were no changes in host carcass weight, food intake, plasma albumin, hematocrit or white blood cell counts. Platelet suppression was associated with the 1,000- and 2,000-mg doses with the 12-day treatment. Morphometry of the small intestine revealed mild but significant shortening of villi in the duodenum and jejunum at the 2,000-mg dose, but none of the animals developed diarrhea. The 500-mg DFMO dose reduced the rate of tumor growth without inducing platelet suppression or altering intestinal morphology. A decrease in RBC putrescine levels was noted at all doses. RBC spermidine levels increased with the 500-mg dose. RBC spermine levels were higher at all doses compared with controls. These results suggest that thrombocytopenia is the major dose-limiting side-effect of continuous DFMO infusion but does not occur at a dose of 500 mg/kg body wt/day.

Concentrations of polyamines in umbilical blood.

Red blood cell and plasma polyamines in umbilical and maternal blood at delivery were measured using high performance liquid chromatography. The concentration of each polyamine in red blood cells and plasma of umbilical blood was significantly higher than in maternal blood. Spermidine and spermine concentrations in fetal red blood cells decreased markedly with the progress of pregnancy. In addition, younger red blood cells contained more polyamines than older cells. Red blood cell polyamines are closely associated with the cell membrane. Plasma polyamine in umbilical blood reflect active fetal metabolism, whereas red blood cell polyamines mainly reflect alterations in erythropoiesis in bone marrow and may indicate the proliferation of the bone marrow.

Diagnosit value of erythrocyte-free polyamines and histaminemia in malignant hepatic tumors and in liver cirrhosis

The present study tries to evaluate the diagnosit value in malignant hepatic tumors of polyamines, of which the relationship with cellular kinetics is known, and histamine, of which catabolism follows a similar pathway. One hundred and fifty six patients were studied: 53 with malignant liver tumors (27 primary, 26 metastatic) and 103 with non-tumoral liver diseases of which 65 were cirrhotic and 38 non-cirrhotic. Erythrocyte polyamines (spermidine and spermine) and histamine levels were assayed. The results indicate the following. 1. Polyamine levels were significantly increased (a) in cirrhotic patients, not only when compared with controls ( p < 10 −8), but also when compared with the non-cirrhotic patients ( p < 10 −7); (b) in primary malignant hepatic tumors ( p < 10 −3). 2. Histamine was significantly increased (a) in the non-tumoral liver diseases ( p < 10 −4), but with no difference between cirrhotic and non-cirrhotic patients; (b) in the secondary malignant tumor patients, histamine levels were lower than in primary tumor patients ( p < 0.04). 3. There was no correlation, in all groups studied, between polyamine and histamine levels. These results suggest the following practical implications. 1. For non-tumor liver diseases, appreciably increased polyamine levels may represent a further argument favoring a cirrhotic condition. 2. In diagnosing hepatic scintigraphic defects, inbetween histamine and polyamines, are in favor of histamine synthesis. In the secondary malignant hepatic tumor group, histamine levels were low. sometimes considerably. Future studies, by estimating plasma diamine oxidase activity may he able to solve some of these questions. In conclusion, the evaluation of erythrocyte polyamine and histamine levels has two practical implications in hepatology. For non-tumor liver diseases, appreciably increased red blood cell polyamine levels may represent a further argument favoring a cirrhotic condition. In diagnosing hepatic scintigraphic defects, increased erythrocyte polyamine levels would suggest a primary malignant hepatic tumor; low histamine levels are more in favor of a secondary malignant hepatic process.

Red blood cell polyamines in mice bearing the Lewis lung carcinoma (3LL) and in patients with bronchopulmonary cancers.

Experimentally, during Lewis lung carcinoma (3LL) growth, the red blood cell (RBC) polyamine levels increase with tumor volume and are inversely correlated to tumoral concentrations of spermidine and spermine. The RBC level of spermidine is continually correlated to both the volume and the tumoral concentration of this polyamine. Clinically, high levels of RBC polyamine are observed in cases of squamous-cell carcinoma or anaplastic cancer, and not in cases of adenocarcinoma. RBC polyamine levels only permit the establishment of statistical differences between groups of patients. Therefore, clinical use of these molecules as tumor markers depends on an understanding of polyamine distribution within blood.

Alterations of red blood cells' polyamines during pregnancy and neonatal period.

Red blood cell polyamines were measured using high-performance liquid chromatography. Spermidine and spermine continued to increase with pregnancy and retained a high level during 24-35 weeks of gestation, then decreased at term; putrescine, however, kept the low nonpregnant level during pregnancy and puerperium. At delivery, umbilical blood showed a significantly higher polyamine level than maternal blood (p less than 0.005 or p less than 0.001). In the neonatal period, each polyamine showed a slight increase on the 1st day after birth, then spermidine and spermine decreased day by day, but putrescine kept the same level. Alterations of polyamines seemed to have some relation to the erythropoiesis in bone marrow and rapid cell proliferations.